Acetazolamide

Aka: Acetazolamide, Diamox, Systemic Carbonic Anhydrase Inhibitor

1. Mechanism
   1. Diuretic in the Carbonic Anhydrase Inhibitor Class
   2. Decreases secretion of Aqueous Humor (Glaucoma)
   3. Decreases Hydrogen Ion at renal proximal tubule
      1. Prevents renal bicarbonate reuptake resulting in urine alkalization (and blood acidification)
      2. Increased renal excretion of Sodium, Potassium, bicarbonate and water
      3. Results in hypokalemic Metabolic Acidosis and Respiratory Alkalosis (mechanism in High Altitude Illness)
         1. Lower resting PaCO2
         2. Higher resting Minute Ventilation
         3. Increased PaO2
2. Indications
   1. High Altitude Sickness treatment and prevention
   2. Pseudotumor Cerebri
   3. Glaucoma
      1. Intraocular Carbonic Anhydrase Inhibitor
         1. Open Angle Glaucoma
      2. Systemic Acetazolamide (IV or oral) Indications
         1. Acute angle closure Glaucoma before surgery
         2. Acute exacerbation of chronic Open Angle Glaucoma
   4. Other indications
      1. Periodic Paralysis
      2. Marfan Syndrome related dural ectasia
      3. Stable Hypercapnic Respiratory Failure (respiratory stimulant)
      4. Epilepsy
         1. FDA approved for Seizures since 1956
         2. Has been used for Catamenial Epilepsy, Myoclonic, Absence and Generalized Seizures
         3. Reiss (1996) Ann Pharmacother 30(5):514-9 [PubMed]
3. Contraindications
   1. Sulfonamide Allergy or Anaphylaxis
   2. Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis history
   3. Hyponatremia
   4. Hypokalemia
   5. Hyperchloremic Metabolic Acidosis
   6. Adrenal Insufficiency
   7. Cirrhosis or other severe liver disease
   8. Severe renal disease
4. Dosing
   1. High Altitude Sickness
      1. Prevention
         1. Adults: 125 mg orally every 12 hours (FDA approved)
            1. Up to 250 mg twice daily may be used (but 125 mg is typically sufficient)
            2. Doses of 1000 mg/day (with added Dexamethasone) have been used for rapid ascent (e.g. rescue)
         2. Children: 2.5 mg/kg up to 125 mg every 12 hours (off-label)
         3. Start 24 hours before ascent
         4. Continue for 72 hours or until acclimitization to highest sleeping altitude
      2. Insomnia at altitude: 125 mg orally at bedtime
      3. Treatment: Adults
         1. Start: 250 mg orally twice daily
         2. Range: 500 to 1000 mg/day divided every 8 to 12 hours (every 12 to 24 hours if extended release)
         3. Often used in combination with Dexamethasone
   2. Pseudotumor Cerebri
      1. Dose range: 125-250 mg orally daily to three times daily
   3. Open Angle Glaucoma acute exacerbation or Acute Narrow Angle Glaucoma prior to surgery
      1. Dose: 250 mg orally or IV every 4-6 hours (maximum 1 gram/day)
5. Adverse Effects: Common
   1. Hypokalemia
   2. Hyponatremia
   3. Metabolic Acidosis
   4. Peripheral Paresthesias (common)
   5. Polyuria
   6. Taste Dysfunction (Dysgeusia) with bitter or Metallic Taste
   7. Headache
   8. Nausea or Vomiting
   9. Abdominal Cramping
   10. Black Stool
   11. Diarrhea
   12. Fatigue
   13. Drowsiness
   14. Depressed Mood
   15. Decreased Libido
   16. Ureteral Stones
6. Adverse Effects: Uncommon Serious
   1. Stevens-Johnson Syndrome
   2. Anaphylaxis
   3. Blood Dyscrasias
7. Drug Interactions
   1. Cyclosporine
   2. Salicylates
8. Safety
   1. Pregnancy Category C
9. References
   1. Olson (2020) Clinical Pharmacology, Medmaster, Miami, p. 62-3
   2. Hamilton (2010) Tarason Pocket Pharmacopeia, p. 224
   3. Lovecchio (2017) Crit Dec Emerg Med 31(8): 28
   4. Lovecchio (2022) Crit Dec Emerg Med 36(3): 28